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Medium-chain triglycerides
Octanoic (C8) and Decanoic Acid (C10)
The key benefits of the medium-chain triglyceride, decanoic acid otherwise known as C10 are outlined below.
Optimise Mitochodria
Mitochondria are cellular organelles that produce ATP (the brain's energy currency). Hence, the greater the number of mitochondria within the neuronal environment, the more energy there is available to sustain critical cell functions. Functions such as sustain critical cell functions. Functions such as running sodium-potassium pumps,
which are critical in maintaining the resting membrane potential of a cell and normal neural activity.
Decanoic Acid as an Antioxidant
An antioxidant is a substance that can prevent or minimise damage to cells caused by free radicals such as hydrogen peroxide and superoxide. For example, catalase is a crucial antioxidant responsible for decomposing hydrogen peroxide into water and oxygen. Glutathione is another vital brain antioxidant,
which can broadly reduce free radicals (making them harmless).
The MCT, decanoic acid, has been found to increase both catalase activity in neuronal cells and glutathione levels in glial cells - known for their shuttling capacity.
There are a few receptors that bind glutamate and contribute to the firing of an action potential in the neural environment. AMPA receptors and NMDA receptors are the key targets for glutamate.
During seizure activity, glutamate levels can be elevated significantly - this results in prolonged hyper-excitation. C10 combats this by
Non-competive AMPA receptor inhibitor
acting as a non-competitive AMPA receptor inhibitor. Essentially, C10 binds to AMPA receptors on the post synaptic neuron, which competes directly against glutamate. This competition results in less sodium-potassium pumps are being opened, and prevents the post synaptic neuron from depolarising.
Importantly, C10 is not just an AMPA receptor inhibitor but a non-competitive inhibitor. This is relevant for dogs experiencing seizures, which involve large synaptic release of glutamate, and where drugs that act as competitive inhibitors are likely to be less efficacious
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Glutamate
Figure 3: A schematic diagram of AMPA and NDMA receptor interactions with glutamate. (Copyright Cascade Animal Sciences)
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Glutamate
Figure 4: A schematic diagram of decanoic acid's (C10) inhibitory action on AMPA receptors. (Copyright Cascade Animal Sciences)
Regulates protein synthesis and autophagy
A combination of synaptic impairment and neuro-degeneration underpins canine cognitive decline and idiopathic epilepsy. One of the benefits of MCTs is that they help to regulate protein synthesis and autophagy. Autophagy is a process where the body breaks down and recycles damaged cells. This is important for many cellular processes, including maintaining healthy nerve
This is important for many cellular processes, including maintaining healthy nerve cells. A balance between C8 and C10 is particularly important to ensure accumulation of C10 in the cellular environment. C8 is preferentially metabolised by astrocytes over C10, meaning C10 is able to accumulate in the neuronal environment.
Epileptogenesis
Epileptogenesis refers to changes in the brain that propagate recurrent spontaneous seizures activity. It is often exacerbated by disease or trauma that causes inflammation and neuronal cell death. Epileptogenesis is affected by epigenetics changes. Epigenetics changes refer to changes in the genome that are secondary to behavioral or environmental factors and don’t
directly affect DNA sequencing. They can, however, affect how your body reads DNA and the expression of certain genes. These changes are reversible (and could be a point of interest for future therapy development). The most prominent epigenetic process currently reported in the literature are; adenosine-regulated DNA methylation, histone acetylation, and non-coding RNAs.
An examination of hippocampal tissue in rodents that experienced random seizure activity found a reduction in pyruvate dehydrogenase activity, along with other metabolites of the Krebs cycle resulting in glucose hypometabolis. It is no surprise, that glucose hypometabolism results in cells’ diminished ability to form proteins and lipids that are key in neurotransmitter regulation and the prevention of epigenetic changes.
One solution to glucose hypometabolism and subsequent effects includes alternative fuel sources that don’t require pyruvate dehydrogenases (an enzyme that breaks down pyruvate) such as medium-chain fatty acids and ketones bodies.
A combination of synaptic impairment and neuro-degeneration underpins canine cognitive decline and idiopathic epilepsy. One of the benefits of MCTs is that they help to regulate protein synthesis and autophagy. Autophagy is a process where the body breaks down and recycles damaged cells. This is important for many cellular processes,
Regualtes Neuronal growth and synapse stabilisation.
including maintaining healthy nerve cells. A balance between C8 and C10 is particularly important to ensure accumulation of C10 in the cellular environment. C8 is preferentially metabolised by astrocytes over C10, meaning C10 is able to accumulate in the neuronal environment.
